Neoplasia Flashcards
What are the two types of tumors?
Benign and Malignant
What are the characteristics of Benign tumors?
Innocent behavior Localized lesions Don't spread Patient typically survives Surgically removable
What do benign tumors have that malignant tumors don’t have?
a pressed fibrous connective tissue capsule made of stromal cells
What are the characteristics of Malignant tumors?
“cancer”
aggressive behavior
Metastasis
Fibroma is…
Benign tumor of adult fibrous tissue
Myxoma is…
benign tumor of embryonic fibrous tissue
Lipoma is…
Benign tumor of fat
Chondroma is…
Benign tumor of cartilage
Osteoma is…
Benign tumor of bone
Fibrosarcoma is…
Malignant tumor of adult fibrous tissue
Myxosarcoma is…
Malignant tumor of embryonic fibrous tissue
Liposarcoma is…
Malignant tumor of fat
Chondrosarcoma is…
Malignant tumor of Cartilage
Osteosarcoma is…
Malignant tumor of bone
Hemangioma is…
Benign tumor of blood vessels
Lymphangioma is…
Benign tumor of lymph vessels
Hemangiosarcoma/angiosarcoma is…
Malignant tumor of blood vessels
Lymphangiosarcoma is…
Malignant tumor of lymph vessels
Leiomyoma is…
Benign tumor of smooth muscle
Rhabdomyoma is…
Benign tumor of striated muscle
Leiomyosarcoma is..
Malignant tumor of smooth muscle
Rhabdomyosarcoma is…
Malignant tumor of striated muscle
Papilloma, Seborrheic Keratosis, and some skin adnexal tumors are…
benign tumors of stratified squamous epithelial tissue
Adenoma is…
Benign tumor of Glandular Epithelium
Hepatic Adenoma, Renal Tubular adenoma, and Bile duct adenoma are…
Benign tumor of Liver, kidney and Bile duct
Squamous cell carcinoma, epidermoid carcinoma and some skin adnexal tumors are…
Malignant tumors of stratified squamous epithelial tissue
Adenocarcinoma is..
Malignant tumor of Glandular Epithelium
Hepatoma, hepatocellular carcinoma, renal cell carcinoma, hypernephroma cholangiocarcinoma are…
Malignant tumors of Liver, Kidney, and bile duct
Transitional cell papilloma is…
Benign tumor of transitional epithelium
Transitional cell carcinoma is…
Malignant tumor of transitional epithelium
Seminoma, embryonal cell carcinoma are..
Malignant tumors of testis
Glioma grades 1-3 anaplastic, glioblastoma grade 4 are…
Malignant tumors of glial cells
Ganglionneuroma is…
Benign tumor of nerve cells
Neuroblastoma and Medulloblastoma are…
malignant tumors of nerve cells
Meningioma is…
Benign tumor of meninges
What are the two basic components of all tumors?
Neoplastic cells
Supporting Stroma
What are neoplastic cells?
constitute the tumor parenchyma
What do neoplastic cells determine?
classification of tumors and their biologic behavior
What is the supporting stroma?
non-neoplastic connective tissue, blood vessels, and adaptive/innate immunity cells
Supports growth and proliferation of tumor cells
Tumor Microenvironment
What does the supporting stroma determine?
how the tumor will grow and proliferate
What does the tumor microenvironment consist of?
Hematopoietic Cells
Cells with Mesenchymal Origin
Non cellular components
What are hematopoietic cells?
cells arising in bone marrow
T and B cells
Natural Killer Cells
macrophages
neutrophils
What are cells with mesenchymal origin?
Fibroblasts Myofibroblasts Mesenchymal stem cells Adipocytes Endothelial Cells
What are the noncellular components of the tumor microenvironment?
ECM:
proteins
glycoproteins
proteoglycans
What is the significance of the tumor microenvironment?
protects cancer cells
Has important influence on the malignancy outcome and treatment responses
What is differentiation?
How closely tumor cells histologically and functionally resemble their normal cell counterpart
What is anaplasia?
lack of differentiation of tumor cells; MALIGNANCY’s HALLMARK
What is metaplasia?
replacement of one cell type with another cell type; normal physiologic response to chronic inflammation
What is dysplasia?
CHAOS; loss of cellular uniformity and architectural organization
What is carcinoma in situ?
Marked dysplastic changes involving the ENTIRE thickness of the epithelium
What is invasive carcinoma?
the basement membrane isn’t intact anymore so the cells can escape and metastasize
What doesn’t have local invasion?
Benign tumors
What is metastasis?
invasion of lymphatics, blood vessels, or body cavities by tumor, followed by transport and growth of secondary tumor cell masses dislodged from the primary tumor
What are pathways of tumor spread?
Seeding of body cavities and surfaces
Lymphatic spread
Hematogenous Spread
Iatrogenic spread
What is seeding of body cavities and surfaces?
disperson into peritoneal, pleural, pericardial, subarachnoid, and joint spaces
Will spread into places that there isn’t a barrier
What is lymphatic spread?
Transport of tumor cells to regional nodes and throughout the body
Mostly associated with carcinomas
What is hematogenous spread?
typical of sarcoma and some carcinomas; metastasis follows the venous flow pattern
What are the most common sites of hematogenous spread?
Lung and liver
What is iatrogenic spread?
when they do a biopsy and the surgical instrument is a tool for seeding the cancer
What is tumor metastatic tropism?
a tumor’s tendency to metastasize to specific organs
indicates the cancer cells ability to adopt to and colonize in the microenvironment of secondary tissues
Which cancers metastasize to the brain?
Lung tumors
breast tumors
Melanoma
What cancers metastasize to the liver?
pancreatic cancer
What cancers metastasize to the bone marrow?
prostate cancer
What are the mechanisms of tropism?
Some tumor cells have adhesion molecules with expression of ligands in a specific organ
Some tumor cells have chemokine receptors in particular organ
Microenvironment of an organ might not be suitable
What are two places that are rarely sites of metastasize?
Skeletal muscle and spleen
What may also determine where tumors metastasize to?
circulation layouts like primary colon cancer following the portal vein drainage from the colon to the liver and causing liver cancer
What are environmental risk factors of cancer?
infectious agents smoking alcohol consumption diet obesity Reproductive history carcinogens
Why is age an important risk factor for cancer?
because as we age we accumulate somatic mutations and have a decline in immune response
What are three acquired predisposing factors in cancer?
chronic inflammation
precursor lesions
Immunodeficiency states
Why does chronic inflammation increase the risk of cancer?
because there is an increased flow of immune response cells to the site which can increase the chance of mutation in that area; ROS are also produced and they damage DNA
Where do precursor lesions occur and why do they increase the risk of getting cancer?
they occur in settings of chronic inflammation and change the cells
What determines whether precursor lesions will be become malignant or not?
there genetic expression pattern
What type of T cell deficiency also increased the risk of cancers?
CD8+
What are the 10 Hallmarks/Characteristics of Cancer?
Sustaining Proliferative Signaling Avoiding Immune Destruction Enabling replicative immortality tumor promoting inflammation Activating invasion and metastasis Genomic instability Inducing angiogenesis Resisting cell death Deregulating cellular energetics
What are the normal steps of cell proliferation?
1) Growth factor binding to cell surface receptor
2) Activation of signal transduction proteins
3) Initiating DNA transcription
What are oncogenes?
genes that promote autonomous cell growth; cancer cells have these
What are protooncogenes?
Genes that inhibit autonomous cell growth
What does tyrosine kinase-mediated signal transduction do in normal cells?
causes cellular growth, apoptosis, and cell migration
In cancer cells, what happens to tyrosine kinase pathway?
The pathway is hyperreactive due to mutations
What causes activation of oncogenes to malignant transformation?
Mutations or Overexpression of MYC oncogenes
How is MYC oncogenes hyperactivated in human tumors?
by translocation between Chromosome 8 and 14
What cancers do MYC oncogenes overexpression cause?
Burkitts lymphoma
B cell lymphoma
Lung cancers
What is Burkitt Lymphoma?
an aggressive type of B cell lymphoma most often in children and young adults
What do tumor suppressor genes do normally?
slow down cell divisions, repair DNA mistakes, and activate apoptosis
What happens to tumor suppresor genes in cancer?
they are inactivated
What is Loss of heterozygosity?
mutation of both alleles of tumor suppressor genes are needed for carcinogenesis
What are examples of LOH?
RB and P53
What does RB gene mutation cause?
persistent cell cycling which contributes to the pathogenesis of childhood tumor Retinoblastoma
What does the TP53 protein normally do?
prevents the growth of genetically defective cells
How does the TP53 protein prevent the growth of genetically defective cells?
Senses DNA damage
Arrests the cell cycle
If DNA can be repaired, the cell undergoes S phase
If DNA cannot be repaired, TP 53 induces apoptosis
What percentage of cancers have a mutated p53 gene?
50%
What is antitumor immunity?
t cell recognition of tumor antigen leading to t cell activation
How does the tumor evade immune response?
Failure to produce tumor antigen causing lack of T cell recognition of tumor
Mutations in MHC genes or genes needed for antigen processing causing lack of T cell Recognition of tumor
Production of immunosuppressive proteins or expressin of inhibotry cell surface proteins causing inhibition of T cell activation
What type of immunity does tumor cells evade?
cell mediated Immunity:
CD8+ T cells
Natural Killer Cells
Macrophages
How do tumor cells enable replicative immortality?
By keeping telomerase active so that the tumor cells telomeres never get so short that they would undergo apoptosis
What is the metastatic cascade?
Invasion of ECM
Vascular disemmination and homing of tumor cells
What are the steps in invasion of ECM?
1) detachment and loosening of intracellular junctions
2) ECM degredation
3) Migration
How is the ECM degraded in the invasion of ECM?
by proteases creating a passage
What are the 4 theories on how metastasis occurs?
1) Clonal evolution model
2) metastasis signature
3) metastatic variants
4) microenvironment
What is the clonal evolution model?
rare variant clones in the primary tumor cause it to metastasize
What does the microenvironment do to cause metastasis?
influences angiogenesis, local invasiveness, and resistance to immune defense of the host
What is genomic instability?
a process of gene alterations which cause DNA repairs to not be fixed and unstable DNA; can increase the risk of cancer
What genes are mutated in breast cancer?
BRCA1 and 2
What gene is mutated in ovarian, prostate, and stomach cancers?
BRCA 2
What is angiogenesis?
new blood vessel growth
What is angiogenesis’ dual effect on tumor growth?
1) stimulates tumor growth through endothelial cell production of growth factors
2) influences metastatic potential
How does angiogenesis increase for tumor cells?
the tumor cells sense hypoxia and this causes upregulation of VEGF which causes angiogenesis
What cells are primed for apoptosis?
Normal cells that have a predominance of PROAPOPTOTIC proteins
What cells are unprimed for apoptosis?
Cancer cells that have a predominance of ANTIAPOPTOTIC proteins
What pathway do cancer cells use to get their energy?
anaerobic respiration because they don’t have a lot of oxygen and they can move faster because this pathway only creates two molecules of ATP
What are the two steps involved in chemical carcinogenesis?
1) Initiation
2) Promotion
What is initiation of chemical carcinogenesis?
induction of IRREVERSIBLE mutations in the genome
Can be direct acting agents or indirect acting agents
What is promotion of chemical carcinogenesis?
can induce tumors in previously initiated cell by stimulating cellular proliferation
short lived, REVERSIBLE, and non-tumorigenic by themselves
What are direct acting agents of initiation?
They don’t need metabolic activation; need to be cautious
What are indirect acting agents of initiation?
They do need metabolic activation; ex. polycyclic hydrocarbons
What are two types of radiation carcinogenesis?
UV rays of sunlight
Ionizing Radiation
What are some forms of ionizing radiation?
Xrays, gamma rays
What are the most toxic, mutagenic, and carcinogenic UV light induced DNA photoproducts?
Cyclobutane Pyrimidine Dimers (CPDs)
6-4) pyrimidine-pyrimidone photoproducts (6-4PPs
What causes the most prominent damage to our macromolecules?
UVB rays
How does UVB rays damage our macromolecules?
damages DNA by creating pyrimidine dimers that create a kink in the DNA structure
What does UVA rays create?
ROS
Which type of UV rays is there no protection for?
UVA rays
How does ionizing radiation cause cancer?
1) damages the nucleotides or DNA sugar molecules
2) causes strand breaks in DNA
3) indirect DNA damage by increasing ROS in cell
Both benign and malignant tumors cause problems by?
Location and impingement on adjacent structures
Functional activity such as hormone production
Bleeding and Infection
Symptoms from tumor rupture or infection
Cachexia
What are effects of locally located tumors?
Intracranial tumors can expand and destroy things around them like the pituitary
GI tract tumors may cause obstruction of the bowel or ulcerate
What effect does hormone production of tumors have?
causes pareneoplastic syndrome such as hypoglycemia or hypercalcemia
What is cancer cachexia?
weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current body weight and height
profound loss of muscle mass and fat
What are the stages of cancer Cachexia?
Precachexia
Cachexia
Refractory Cachexia
What causes Cancer Cachexia?
multifactorial causes but NOT caloric intake
What is the pathophysiology of cancer cachexia?
underlying chronic inflammation causing a hypermetabolic state
What is a widely accepted cytokine associated with cancer cachexia?
TNF alpha
What is associated with cancer cachexia?
lipolysis and lipid mobilizing factor
What is paraneoplastic Syndrome?
tumor associated syndromes where the symptoms are not directly related to the spread of the tumor
The earliest clinical manifestations of a neoplasm and can mimic distant spread
What are the 4 tumor associated syndromes that the patients can develop?
Endocrinopathies
Paraneoplastic Neurologic Syndromes
Thrombotic Diatheses
Hypercalcemia
What are paraneoplastic endocrinopathies?
non-endocrine cancers that produce hormones or hormone like factors
Small cell lung cancer causes what disease by releasing ACTH?
Cushings
What percentage of patients with Cushing syndrome have lung carcinomas?
50%
What is the most common paraneoplastic syndrome?
Hypercalcemia
What tumors are associated with paraneoplastic hypercalcemia?
Breast
Lung
Kidney
Ovary
What are paraneoplastic neurologic syndromes?
heterogenous group of disorders caused by mechanisms other than metastases, metabolic, and nutritional deficits, infections, coagulopathy, or side effects of cancer treatment
What is the pathogenesis of paraneoplastic neurologic syndromes?
there are antibodies in the serum or CSF of the cancer patients
What two types of antibodies are found in paraneoplastic neurologic syndromes?
Antibodies directed against intracellular neuronal proteins
Antibodies directed against neuronal cell surface or synaptic proteins
What are antibodies directed against intracellular neuronal proteins?
well characterized and have association with cancer in the body
Hu/ANNA-1
Ri/ANNA-2
What are antibodies directed against neuronal cell surface or synaptic proteins?
aren’t always associated with cancer
NMDA receptor
What is paraneoplastic thrombotic diatheses?
a vicious cycle between activation of the platelet and tumor growth that feed off of eachother
What is the pathogenesis of paraneoplastic thrombotic diatheses?
1) Tumor stimulates TPO
2) platelet production is increased
3) activated platelets form a shield around the tumor cells
4) platelets also increase metastasis by stimulating angiogenesis
What is tumor grading?
degree of differentiation
Higher grade are more aggressive than lower grade
What is tumor staging?
Size and spread of primary tumor
What are low grade tumors?
Well differentiated
What are high grade tumors?
undifferentiated
What system is used for staging?
TNM system
What does the T stand for in staging?
primary tumor (T1-4)
What does the N stand for in staging?
regional lymph node involvement (N1-4)
What does the M stand for in staging?
metastases (M0, M1)
What methods do we have for laboratory diagnosis of cancer?
Histologic and Cytological methods Fine needle aspiration Flow cytometry Immunohistochemistry Circulating tumor cells
What ways can laboratory evaluation of a lesion be done?
Excision or biopsy
Fine Needle Aspiration
Cytologic Smears
What is the most important method of diagnosis?
Histologic examination
What must be confirmed by a biopsy?
Cytologic diagnosis
What is fine needle aspiration (FNA)?
involves apsiration of cells and fluids from tumor or masses taht are palpable
Where can FNA be performed?
breast
thyroid
lymph nodes
What is cytologic smears?
involve examination of exfoliated cells like in PAP smears
What is flow cytometry?
measures the presence of membrane antigens or DNA content of tumor cells
What cancers use flow cytometry?
Leukemia
Lymphoma
What is immunohistochemistry?
detects cell products or surface markers using specific antibodies
What is imunohistochemistry used for?
Diagnosis of undifferentiated tumors
Determination of site of origin of metastases
Detection of molecules with prognostic or therapeutic significance
What are circulating tumor cells?
are a subpopulation of tumors cells originated from the primary cancer
They assist in monitoring and predicting cancer progression and evaluating treatment
What do circulating tumor cells have the ability to do?
disseminate and proliferate as a metastatic lesion
